Diseases of the central nervous system (CNS) present a prevalent and ever-increasing burden for the world healthcare industry. For example, Alzheimer's disease is diagnosed in an estimated 24 million people, a number projected to double every 20 years. Despite such emerging demands for treatment of CNS diseases, only about 7% of CNS drugs in clinical development reach the marketplace, compared to the about 12% average across all therapeutic areas, or about 20% for cardiovascular drugs.
This low success rate is often attributed to a unique CNS structure coined as the blood-brain barrier (BBB), which introduces a pharmacokinetic hurdle by blocking compounds from entering brain tissues from capillaries. Only compounds smaller than about 500 Da easily cross the BBB, but few CNS diseases may consistently respond to this category of molecules.
Because the BBB blocks nearly all polar or large compounds, new drug treatments for the CNS of higher molecular weight must take BBB function into account, which, in turn, may require more extensive pre-clinical studies.